Inhibition of Autonomous Human Keratinocyte Proliferation and Amphiregulin Mitogenic Activity by Sulfated Polysaccharides

• Published in: In Vitro Cellular & Developmental Biology - Animal 1992-03, Vol.28A (3), p.218-222
• Main Authors: Paul W. Cook, Paul A. Mattox, Winifred W. Keeble, Shipley, Gary D.
• Format: Article
• Language: English
• Subjects: Amphiregulin; Biological and medical sciences; Cell culture techniques; Cell Division - drug effects; Cell growth; Cell lines; Cell physiology; Cells, Cultured; Chondroitin Sulfates - pharmacology; Dextran Sulfate - pharmacology; Dextrans; EGF Family of Proteins; Epidermal Growth Factor - pharmacology; Epithelial cells; Fundamental and applied biological sciences. Psychology; Glycoproteins - antagonists & inhibitors; Growth Substances - pharmacology; Heparin; Heparin - pharmacology; Heparitin Sulfate - pharmacology; Humans; Intercellular Signaling Peptides and Proteins; Keratinocytes; Keratinocytes - cytology; Keratinocytes - drug effects; Molecular and cellular biology; Polysaccharides; Polysaccharides - pharmacology; Rapid Communications in Cell Biology; Responses to growth factors, tumor promotors, other factors; Sulfates; Sulfation
• ISSN: 0883-8364; 2327-431X; 1543-706X
• DOI: 10.1007/BF02631096

We previously demonstrated that human keratinocyte cultures proliferate in the absence of polypeptide growth factors (autonomous growth) and that this autonomous growth is blocked by interaction of heparin with a human keratinocyte-de- rived autocrine factor (KAF) which we identified as amphiregulin (AR). In the present study, we demonstrate that sulfated polysaccharides other than heparin (low and high molecular weight dextran sulfates) also inhibit the AR-mediated autonomous proliferation of human keratinocytes. Furthermore, sulfated polysaccharides such as high and low molecular weight dextran sulfates, heparan sulfate and, to a lesser extent, chondroitin sulfates B and C were also shown to be inhibitors of human keratinocyte-derived AR (k-d AR)-stimulated DNA synthesis in quiescent murine AKR-2B cell cultures. Our results demonstrate that sulfation of polysaccharides is required for AR inhibitory activity, and that several sulfated polysaccharides (other than heparin) can act as inhibitors of AR-mediated autonomous proliferation in human epidermal keratinocytes and as inhibitors of k-d AR-mediated mitogenic activity in AKR-2B cells.